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Innate immune response of LTBI+HIV+ children

Award Number: R01AI142672
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/14/2020
PERIOD OF PERFORMANCE END DATE: 01/31/2026

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Innate immune response of LTBI+HIV+ children - Mycobacterium tuberculosis (Mtb) infects one-third of the world’s population and causes almost 1.3 million deaths per year, including 100, 000 children. Approximately 90% of infected persons have latent tuberculosis infection (LTBI), have protective immunity and remain well, but 10% develop primary tuberculosis (TB) soon after infection or reactivation TB many years later. Children are more susceptible to TB infection, due to an immature immune system. HIV infection in children markedly increases susceptibility to TB, and HIV-infected persons with LTBI have an 800-fold greater risk of developing active TB (www.cdc.gov/tb/). TB is the leading cause of death in HIV-infected persons and more than half a million coinfected people die annually. To develop adequate prophylaxis or therapy, it is important to understand immune responses to Mtb. Identification of HIV+ children with LTBI who are at greatly increased risk for development of TB would allow treating only high-risk children, facilitating completion of therapy for LTBI and preventing future development of TB. To identify these children, it is important to pinpoint the nature of the defective immune responses that permit development of active TB in HIV+LTBI+ pediatric patients. Over the past 18 years, we have published a series of articles demonstrating that human NK cells have the potential to contribute to both innate and adaptive immune responses to Mtb. Our recently published studies demonstrate that memory-like NK cells contribute to vaccine-induced protective immunity against Mtb and IL-21 is required for expansion of memory-like NK cells in both humans and mice. Based on our published studies, we hypothesize that HIV-LTBI+ children household contacts have defective memory-like NK cell expansion compared to HIV-LTBI+ adult household contacts and these defects are more severe in HIV+ LTBI+ children. The proposed studies in the current application will be performed in India as a part of RePORT-India consortium. This study will leverage the large Indo-US investment and TB/HIV research consortium of RePORT-India which has developed cohorts of TB cases and household contacts in India and has paired Indian investigators with US investigators at 6 sites. Already collected samples will be used for the proposed studies in aim 1. Our specific aims are: 1. Determine Mtb specific memory-like NK cell responses of children in a large group of household contacts of TB patients. 2.Compare the memory-like NK cell responses of HIV+ and HIV- children with LTBI. 3. Determine whether KIR haplotypes and HLA polymorphism is associated with expansion of memory-like NK cells in children.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $0 )
2025	2024	THE UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT TYLER	11937 US HIGHWAY 271	TYLER	TX	75708	SMITH	USA	Allergy and Infectious Diseases Research	001	4	2/12/2025	NON-COMPETING CONTINUATION	-$1
2025	2024	SAINT LOUIS UNIVERSITY	221 N GRAND BLVD	SAINT LOUIS	MO	63103	SAINT LOUIS CITY	USA	Allergy and Infectious Diseases Research	003	5	3/31/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2025	2024	SAINT LOUIS UNIVERSITY	221 N GRAND BLVD	SAINT LOUIS	MO	63103	SAINT LOUIS CITY	USA	Allergy and Infectious Diseases Research	002	5	2/12/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$305,214
2025	2022	THE UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT TYLER	11937 US HIGHWAY 271	TYLER	TX	75708	SMITH	USA	Allergy and Infectious Diseases Research	000	3	2/12/2025	NON-COMPETING CONTINUATION	-$305,213
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $726,290 )
2024	2024	THE UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT TYLER	11937 US HIGHWAY 271	TYLER	TX	75708	SMITH	USA	Allergy and Infectious Diseases Research	001	4	1/30/2024	NON-COMPETING CONTINUATION	$625,627
2024	2024	SAINT LOUIS UNIVERSITY	221 N GRAND BLVD	SAINT LOUIS	MO	63103	SAINT LOUIS CITY	USA	Allergy and Infectious Diseases Research	004	5	8/14/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$726,289
2024	2024	THE UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT TYLER	11937 US HIGHWAY 271	TYLER	TX	75708	SMITH	USA	Allergy and Infectious Diseases Research	002	4	7/2/2024	NON-COMPETING CONTINUATION	$69,513
2024	2024	THE UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT TYLER	11937 US HIGHWAY 271	TYLER	TX	75708	SMITH	USA	Allergy and Infectious Diseases Research	003	4	8/14/2024	NON-COMPETING CONTINUATION	-$695,139
2024	2022	THE UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT TYLER	11937 US HIGHWAY 271	TYLER	TX	75708	SMITH	USA	Allergy and Infectious Diseases Research	000	3	1/11/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $726,290

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2022	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT TYLER, THE	11937 US HWY 271	TYLER	TX	75708	SMITH	USA	Allergy and Infectious Diseases Research	000	3	9/6/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $695,140 )
2022	2022	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT TYLER, THE	11937 US HWY 271	TYLER	TX	75708	SMITH	USA	Allergy and Infectious Diseases Research	000	3	8/19/2022	NON-COMPETING CONTINUATION	$695,140
														Subtotal = $695,140

Issue Date FY: 2021 ( Subtotal = $695,140 )
2021	2021	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT TYLER, THE	11937 US HWY 271	TYLER	TX	75708	SMITH	USA	Allergy and Infectious Diseases Research	000	2	8/16/2021	NON-COMPETING CONTINUATION	$695,140
														Subtotal = $695,140

Issue Date FY: 2020 ( Subtotal = $718,640 )
2020	2020	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT TYLER, THE	11937 US HWY 271	TYLER	TX	75708	SMITH	USA	Allergy and Infectious Diseases Research	000	1	9/14/2020	NEW	$718,640
														Subtotal = $718,640

Grand Total All Awards = $2,835,210

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Innate immune response of LTBI+HIV+ children

Award Number: R01AI142672

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/14/2020

PERIOD OF PERFORMANCE END DATE: 01/31/2026

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